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评价不同的总美洲利什曼原虫抗原,以开发第一代疫苗,该疫苗用 Toll 样受体 3 激动剂配制,用于预防皮肤利什曼病。

Evaluation of different total Leishmania amazonensis antigens for the development of a first-generation vaccine formulated with a Toll-like receptor-3 agonist to prevent cutaneous leishmaniasis.

机构信息

Instituto de Medicina y Biología Experimental de Cuyo, Universidad Nacional de Cuyo, Consejo Nacional de Investigaciones Científicas y Tecnológicas, Mendoza, Argentina.

Instituto de Patología Experimental, Consejo Nacional de Investigaciones Científicas y Tecnológicas, Salta, Argentina.

出版信息

Mem Inst Oswaldo Cruz. 2020;115:e200067. doi: 10.1590/0074-02760200067. Epub 2020 Jul 13.

Abstract

BACKGROUND Unfortunately, no any vaccine against leishmaniasis has been developed for human use. Therefore, a vaccine based on total Leishmania antigens could be a good and economic approach; and there are different methodologies to obtain these antigens. However, it is unknown whether the method to obtain the antigens affects the integrity and immune response caused by them. OBJECTIVES to compare the protein profile and immune response generated by total L. amazonensis antigens (TLA) produced by different methods, as well as to analyse the immune response and protection by a first-generation vaccine formulated with sonicated TLA (sTLA) and polyinosinic:polycytidylic acid [Poly (I:C)]. METHODS TLA were obtained by four different methodologies and their integrity and immune response were evaluated. Finally, sTLA was formulated with Poly (I:C) and their protective immune response was measured. FINDINGS sTLA presented a conserved protein profile and induced a strong immune response. In addition, Poly (I:C) improved the immune response generated by sTLA. Finally, sTLA + Poly (I:C) formulation provided partial protection against L. amazonensis infection. MAIN CONCLUSIONS The protein profile and immune response depend on the methodology used to obtain the antigens. Also, the formulation sTLA + Poly (I:C) provides partial protection against cutaneous leishmaniasis in mice.

摘要

背景

不幸的是,目前还没有针对人类使用的利什曼病疫苗。因此,基于全利什曼抗原的疫苗可能是一种良好且经济的方法;并且有不同的方法来获得这些抗原。然而,目前尚不清楚获得抗原的方法是否会影响其完整性和免疫反应。目的:比较不同方法获得的总美洲利什曼原虫抗原(TLA)的蛋白图谱和免疫反应,以及分析用超声处理的 TLA(sTLA)和聚肌苷酸:聚胞苷酸[聚(I:C)]配制的第一代疫苗引起的免疫反应和保护作用。方法:用四种不同的方法获得 TLA,并评估其完整性和免疫反应。最后,用聚(I:C)配制 sTLA,并测量其保护性免疫反应。结果:sTLA 具有保守的蛋白图谱并诱导强烈的免疫反应。此外,聚(I:C)增强了 sTLA 产生的免疫反应。最后,sTLA+聚(I:C)配方为预防美洲利什曼原虫感染提供了部分保护。主要结论:抗原获得方法决定了蛋白图谱和免疫反应。此外,sTLA+聚(I:C)配方可为小鼠提供对皮肤利什曼病的部分保护。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52ea/7357544/45eca5058ad6/1678-8060-mioc-115-e200067-gf1.jpg

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